Antiphospholipid (aPL)-Positive
Conditions
Keywords
Antiphospholipid (aPL)-positive, Antiphospholid syndrome (APS)
Brief summary
The primary purpose of this study was to evaluate the safety and tolerability of intravenous (IV) ALXN1007 in persistently antiphospholipid (aPL)-positive patients with at least 1 of the following non-criteria manifestations of APS: aPL-nephropathy, skin ulcers and/or thrombocytopenia.
Interventions
BIOLOGICALStudy Drug- ALXN1007
10 mg/kg IV q 2 weeks x 12 doses
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients with a persistent and clinically significant aPL profile Patients with at least 1 of the following non-criteria manifestations of APS: 1. aPL-nephropathy (diagnosed by kidney biopsy within 12 months of Screening) confirmed based on the updated APS Classification Criteria recommendations, and urine protein to creatinine ratio \> 1.0 at the time of the Screening visit and/or 2. Skin ulcers (non-infected livedoid vasculitis-like skin ulcer and/or large skin ulceration resembling pyoderma gangrenosum) for at least 4 weeks prior to the Screening visit, diagnosed by physical examination, and/or 3. Persistent active thrombocytopenia (diagnosed by platelet counts \<100 x 103/μL and ≥20 x 103/μL \[SI: \<100 x 109/L and ≥ 20 x 109/L\]) and confirmed at the time of screening (at least 4 weeks after previous test) based on the updated APS Classification Criteria recommendations Patients and spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method) starting at Screening and continuing through the entire study. Patients with aPL-nephropathy must be receiving or agree to initiate an ACE inhibitor or angiotensin receptor blocker at least 4 weeks prior to initiation of ALXN1007 treatment; unless patient is documented to be intolerant. Patients receiving oral corticosteroids must be on a stable dose of ≤ 10 mg/day of prednisone or equivalent dose of another corticosteroid preparation for at least 4 weeks prior to the first dose of ALXN1007. Patients receiving immunosuppressive medications (including but not limited to methotrexate, hydroxychloroquine, azathioprine, cyclosporine and mycophenolate mofetil) must be on a stable dose for at least 4 weeks prior to the first dose of ALXN1007. Patients receiving oral anticoagulants or antiplatelet agents (including but not limited to aspirin) must be on stable doses for at least 4 weeks prior to first dose of ALXN1007. Patients must be willing and able to give written informed consent and to comply with all study visits and procedures.
Exclusion criteria
Patients meeting the ACR classification criteria for systemic lupus erythematosus, systemic sclerosis or other systemic autoimmune diseases other than Primary APS. Patients experiencing an acute thrombosis or a Major Adverse Vascular Event (MAVE) within 12 weeks prior to first administration of ALXN1007. Patients with skin ulcers from causes other than aPL or who are positive for DVT or venous insufficiency at Screening. Patients with renal function status requiring chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy). Patients with unresolved meningococcal disease or with known active bacterial, viral, fungal, mycobacterial or other infection. Patients that have received IVIg treatment within 4 weeks prior to first dose of ALXN1007. Patients that have received a course of rituximab (RITUXAN®) therapy within 12 months prior to first dose of ALXN1007 or have evidence of persistent depletion of the targeted lymphocyte population. Women who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability of Intravenous (IV) ALXN1007 as Measured by Percentage of Patients Reporting Adverse Events | Treatment Period (24 weeks) |
Countries
Brazil, France, Italy, Japan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALXN1007- Open Label Study ALXN1007
ALXN1007: 10 mg/kg IV q 2 weeks x 12 doses | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period | Adverse Event | 1 |
| Treatment Period | Physician Decision | 1 |
Baseline characteristics
| Characteristic | ALXN1007- Open Label Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment France | 2 participants |
| Region of Enrollment Italy | 1 participants |
| Region of Enrollment Japan | 2 participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 8 / 9 |
| serious Total, serious adverse events | 2 / 9 |
Outcome results
Primary
Safety and Tolerability of Intravenous (IV) ALXN1007 as Measured by Percentage of Patients Reporting Adverse Events
Time frame: Treatment Period (24 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1007 | Safety and Tolerability of Intravenous (IV) ALXN1007 as Measured by Percentage of Patients Reporting Adverse Events | 8 Participants |